pH-Sensitive Drug Delivery System Based on Mesoporous Silica Modified with Poly-L-Lysine (PLL) as a Gatekeeper.

In this work, we synthesized a novel pH-triggered drug delivery system to enhance the bioavailability of the anticancer drug doxorubicin (DOX) through the gatekeeper poly-L-lysine (PLL) on the pore entrances of mesoporous silica nanoparticles (MSNs). Firstly, mesoporous silica was selected as the inorganic support for drug loading. Secondly, PLL was employed as the gatekeeper to control the cargo transport. In a neutral environment, the PLL brushes became shrunken and formed a dense barrier on the pore entrances of PLL/MSNs, which closed the pores and thus prevented the release of cargo. In an acidic environment, the cargo was released from the carrier PLL/MSNs because the pore entrances were opened by the swollen PLL brushes. The DOX-loaded PLL/MSNs (PLL/MSNs-DOX) showed 1.5 times higher drug release under acidic condition (pH = 4) than under neutral condition (pH = 7). During the drug release experiment for 48 h under acidic condition, PLL/MSN-DOX released about 50% of the drug after 9 h and approximately 85% after 24 h, whereas pristine MSNs loaded with DOX (MSNs-DOX) released about 50% of the drug after 30 min and reached equilibrium after 24 h. The MSNs also demonstrated their effectiveness in storing anticancer drugs until the desired environmental trigger is present. Therefore, the pH-responsive MSNs have great potential as a targeting cancer therapy.